REVIEW published: 12 February 2019 doi: 10.3389/fendo.2019.00062 Netting the Stress Responses in Fish Joan Carles Balasch* and Lluís Tort Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain In the last decade, the concept of animal stress has been stressed thin to accommodate the effects of short-term changes in cell and tissue physiology, major behavioral syndromes in individuals and ecological disturbances in populations. Seyle’s definition of stress as “the nonspecific (common) result of any demand upon the body” now encompasses homeostasis in a broader sense, including all the hierarchical levels in a networked biological system. The heterogeneity of stress responses thus varies within individuals, and stressors become multimodal in terms of typology, source and effects, as well as the responses that each individual elicits to cope with the disturbance. In fish, the time course of changes after stress strongly depends on several factors, including the stressful experiences in early life, the vertical transmission of stressful- prone phenotypes, the degree of individual phenotypic plasticity, the robustness and variety of the epigenetic network related to environmentally induced changes, and the intrinsic behavioral responses (individuality/personality) of each individual. The hierarchical heterogeneity of stress responses demands a code that may decrypt and simplify the analysis of both proximate and evolutionary causes of a particular stress phenotype. We propose an analytical framework, the stressotope, defined as Edited by: an adaptive scenario dominated by common environmental selective pressures that Vance L. Trudeau, elicit common multilevel acute stress-induced responses and produce a measurable University of Ottawa, Canada allostatic load in the organism. The stressotope may constitute a blueprint of embedded Reviewed by: interactions between stress-related variations in cell states, molecular mediators and Weiqun Lu, Shanghai Ocean University, China systemic networks, a map of circuits that reflect the inherited and acquired stress Terrence Deak, responses in an ever-changing, microorganismal-loaded medium. Several features Binghamton University, United States of the proposed model are discussed as a starting point to pin down the maximum *Correspondence: Joan Carles Balasch common stress responses across immune-neuroendocrine relevant physiological levels joancarles.balasch@uab.es and scenarios, including the characterization of behavioral responses, in fish. Keywords: stress, stressotope, fish, teleost, plasticity, transcriptomics, phenomics Specialty section: This article was submitted to Experimental Endocrinology, a section of the journal INTRODUCTION Frontiers in Endocrinology When studying the adaptive ecophysiology of stress in teleosts, the largest group of fishes and Received: 08 November 2018 therefore of vertebrates, their extremely diverse life stories appear. This diversity impedes a Accepted: 23 January 2019 Published: 12 February 2019 unified and common description of stress-related effects of environmental insults in fish, and, in consequence, is understandably overlooked in comparative interspecies analyses of stress Citation: Balasch JC and Tort L (2019) Netting physiology. Often, the physiological effects of stressors are treated as species-specific features of the Stress Responses in Fish. the chosen animal, but not always expressly acknowledged as such. Therefore, in the literature, Front. Endocrinol. 10:62. the uncovered stress-related feature of a single or few species becomes, misleadingly, a prominent doi: 10.3389/fendo.2019.00062 characteristic of all teleosts. Frontiers in Endocrinology | www.frontiersin.org 1 February 2019 | Volume 10 | Article 62 Balasch and Tort Netting the Stress Responses in Fish Reducing the exogenous and endogenous covariates that teleosts in terms of the cross-linked interactions between niche elicit stress-related responses undoubtedly helps to reproduce a characteristics, diverse genomic scaffoldings and phenotypic more focused physiological process in the laboratory. However, specificities that define a set of common, multilevel stress this approach veils the adaptive and, more importantly, content- responses in fish. Several endogenous and exogenous features rich interactions between stress-related gene expression and that may be relevant to modeling stressotopes are presented phenotype turnover across the life stories of each species. below as a starting point, by no means exhaustive, to discuss Consequently, the high diversity of teleost lifestyles enriches the the value of this ecophysiological approach to analyze the physiological analysis of stress effects in fish, but also flaws a commonalities to stress responses. unified description of common responses to stress. To overcome this dilemma, the analysis of pan-specific common predictors of stress-related responses should be entrusted to the accurate STRESSING THE STRESS RESPONSES selection of more explanatory variables. For example, when analyzing the effects of high or low temperatures on physiological Although some definitions and general considerations on performance in ectothermic species, choosing species-specific the stress concept involve the idea of an altered status and optimal temperature limits (thermopreferundum) as baseline physiological exceptionality, it is also true that coping with values allows for comparing the effects of common stressors stressors, the stress course, and the response of the organism (1, 2). This approach assumes that the thermic reference are not only a common mechanism but also a very sound and summarizes the adaptive pathway to temperature tolerance conserved response among living species. Hence, the stress evolved in a particular biotope (and, implicitly, part of the responses should be considered as one of the basic and important adaptive life story of each species), and guarantees a more mechanisms that are key to maintain the physiological, cellular realistic description of the “natural” (or eustressed, see below) vs. and molecular stability (homeostasis) of the organism. A myriad maladaptive (distressed) pathways of stress responses. The same of mechanisms available to face the impact of stressors will applies for the comparative inter-species analysis of immune be selected or modulated depending on many factors: the responses to stressors in adult fish, where we should consider species itself, the environmental conditions, and chiefly, the specifically the maturation of primary and secondary immune intensity, duration and predictability of the stressor. Therefore, organs rather than the relative size of fishes. The microorganism an important part of the machinery behind the stress response load may substantially differ between marine and freshwater is the same that is engaged after other stimuli that are not realms, but both environments share the deleterious effects considered stressors, such as reproductive changes, exercise, of the communities of resilient low-abundance pathogens (3). immune stimulants, feeding, light-dark transitions or the Therefore, diverse stress-related physiological adaptations in presence of conspecifics or enrichment objects. That is why teleost inhabiting aquatic biocenosis are to be expected, as well as it is also difficult to make a definition of the stress concept the inter-species commonalities of biological signal transduction with precision. and physiological axes. Given that, the degree of functional Along the years and among the authors that have dealt with maturation of immune-related organs and tissues becomes a the concept of stress (5), several definitions have been provided proxy for adult/mature physiology and allows for the effective following the initial definition, “the non-specific response of the cross-species comparison of immune responses to stress in a body to any demand placed upon it” that was proposed by Hans microbial-rich environment. These examples suggest that when Selye in 1951 (6). Several concepts have been proposed that agree we analyze a particular stress-related phenotype we are not only with the current consensus that stress responses emerge when describing the physiological outcome of specific gene networks, the stimulatory demand exceeds the natural regulatory capacity but also the recapitulation of the evolutionary life-stories of each of an organism (7). For instance, Selye’s eustress and distress (8) individual (Figure 1). responses differentiate between a “normal” state, in which no Considering the complex influences between environmental significant alterations are recorded and the homeostasis is not stressors and pathogen communities, in this short review impaired (although some hormonal, metabolic or molecular we propose a modified biotope concept (4) for analyzing stress-related mechanisms can work), and an “abnormal” state in stress-induced abnormal responses (i.e., capable of inducing which significant alterations are regarded, an overall perception an allostatic load that compromise the evolutionary conserved of alarm occurs and the stress-related mechanisms are highly activation of regulatory stress-related physiological axis engaged. Hormesis has been defined as any process in which a responsive to normal/adaptive stress, see below). This approach cell or an organism exhibits a biphasic response to exposure to would reduce the complexity of species-specific stress analysis increasing amounts of a specific condition (9). It is currently to a set of common descriptors, endogenous and exogenous, applied to chemical stimuli but it has been applied to amounts of such responses. Here, we define a teleost “stressotope” as of sensory stimulus, metabolic alterations and stressors. Thus, an adaptive scenario dominated by common environmental low-dose exposures would elicit a stimulatory, beneficial or selective pressures that elicit common multilevel severe stress- compensatory response (eustress), whereas high doses elicit induced responses and produce a measurable allostatic load in inhibition, alteration or suppression (distress). Likewise, the the organism. term allostasis (10), refers to a concept linked to the energetics Defining the components and dynamics of a stressotope may or the “economy management” of the body resources. Any help to reframe the variability of interspecific stress responses in stressor may lead to an allostatic load that first, compromises the Frontiers in Endocrinology | www.frontiersin.org 2 February 2019 | Volume 10 | Article 62 Balasch and Tort Netting the Stress Responses in Fish FIGURE 1 | Several influences that shape distress-related phenotypes in fish. The analysis of common responses to stress relies on (1) the evolutionary life-stories endured by each species (i.e., genome duplications, changes in stress-related gene pools, changes in oxygen and temperature levels over geologic time and dynamics of extinction/speciation throughout Earth’s history) that constraint the evolvability of biological systems and (2) the pattern and scale of environmental effects in a particular biotope. When analyzing a particular stress-related phenotype the physiological outcomes of specific gene networks during the twin processes of development and growth/metamorphosis have been taken into account, but also the effects of epigenetic transmission of cortisol sensitivity, the differential responses to stressors between sexes and the behavioral interactions within populations as starting points. In this sense, a stressotope defines the boundaries of common pan-specific maladaptive stress responses in a particular/local biotope not only from the perspective of abnormal changes in environmental resources, but also, from the global-scale changes recapitulated in the life story of each individual, i.e., the functional genomics and phenomics of stress intertwined with functional ecology across spatial scales. overall balance of the organism, and second, involves a higher (HPI) axis (11). The SC axis activates a fast stress response, demand of resources that either leads to a higher acquisition of involving the cardio-respiratory system by increasing ventilatory food/energy or induces a number of physiological and metabolic and heart rates, heart stroke volume, and blood perfusion in internal compensations in order to retain the lost balance. This gills and muscle, providing glucose supply to critical tissues, results in maladaptation, which indicates that the regulatory with adrenaline being one of the major mediator hormones. An mechanisms have not been able to compensate the effects of activated HPI axis contribute to the re-organization of resources the stressor. Maladaptation is often associated to chronic stress by increasing the catabolic pathways, supplying glucidic sources, since heavy acute stressors may result in death, and mild ones processing fatty acids for energy, and suppressing other high- in recovery. These chronic stressors leading to maladaptation cost energy and longer-term processes such as those of immune are very relevant in farmed animals, including fish subjected to responses, being plasmatic cortisol levels one of the major artificial conditions. mediators (12). The perception of stress involves the receptor-mediated By binding to glucocorticoid (GR) or mineralocorticoid (MR) sensing of the stressor, either physiologically at neuro-endocrine receptors, cortisol regulates neuroimmunoendocrine circuitries or cellular levels. The perception mechanisms are important, elicits stress-induced immunosuppression and contributes to not only to act as transducers of alarm signals but also to allostatic imbalances. That is why is particularly suited for discriminate the intensity of the stress stimuli and therefore the stress-related surveys in natural and artificial environments and threshold required to trigger the response mechanisms. In fish, the focus of the search for common global markers of stress neuroendocrine signaling affects and becomes regulated by the states in fish. However, the levels of cortisol in distressed fish and, onset of immune responses, due to the peculiar organization of consequently, the individual perception and physiological effects the head kidney, a hematopoietic tissue made from a mixture of the intensity of the stressors, are usually strongly biased for of endocrine, hematopoietic and immune cell populations, neuroendocrine and immune systems in a highly species-specific akin to the mammalian adrenal gland and bone marrow. As manner, which makes the prognosis of stress recovery both in the rest of vertebrates, those responses are mainly mediated apparently simple and dauntingly complex (13). Moreover, by the activation of two hormonal axes in fish, the sympatho- within-species diversity in cortisol levels also differs between chromaffin (SC) axis and the hypothalamic-pituitary-interrenal behavioral phenotypes. As discussed below, selecting for “bold” Frontiers in Endocrinology | www.frontiersin.org 3 February 2019 | Volume 10 | Article 62 Balasch and Tort Netting the Stress Responses in Fish (proactive) and “shy” (reactive) individuals in a population also promote the expression of antioxidant defenses that, if defeated, segregate animals as low- or high-cortisol responders, masking lead to enhanced gene expression that may have distressed the common cortisol-related responses to stress. A side effect outcomes (30). The effects of stress-essential (responsive to of this behavioral phenotyping can be seen in experiments specific stressors) and stress-induced (involved in metabolic and with paired trout, in which agonistic competition for food high order neuroendocrine axis activation) genes (31) reach resources leads to cortisol-based hierarchical social labeling, from cellular disturbances all the way up to systemic processes, with animals ranging from dominant (proactive, usually with and demand a multilevel approach to determine stress sensing low plasmatic cortisol levels) to subordinate (reactive, usually and resolution in a stressotope context. with high plasmatic cortisol levels). When the social status is Notwithstanding the intensity of the stressor, in fish as in other reversed, cortisol levels in former subordinates are recovered vertebrates, the onset of short-term stress mechanisms usually quickly, rendering useless the measure of cortisol levels as a correlates with genome-fixed and protective adaptive responses global long-term common marker of social stress (14). The direct to seasonal and predictable environmental perturbations and effects of social status on plasmatic cortisol levels should also health insults, whereas long-term responses to stressors tend to be balanced out by analyzing the food control exerted by the be considered as harmful expressions of allostatic imbalances dominant conspecifics that may indirectly elevate cortisol levels in an unpredictable or pathogen-ridden environment (32). in food deprived stressed subordinates. This brings the necessity for a broad multilevel framework that Cortisol implants may fail to act as a proxy of behavioral may define more precisely the effect of stressors in cellular, patterns in teleosts (15, 16), and the repeatability of cortisol physiological, pathological/clinical and (eco)systemic scenarios. profiles is higher in reared as opposed to free-living fish due to the artificial control of environmental variables (17). Circadian and seasonal cycles of cortisol secretion must also be considered OVERCOMING THE SCENIC FEAR for assessing the sensitivity and adaptability to stressors (18), considering that cortisol are involved in the synchronization of Ancient and extant biotic and abiotic dynamics of aquatic circadian systems in fish (19). This clearly indicates that a more environments shaped the adaptive/essential stress responses complex multiscale approach (i.e., from cellular activation to of fish in a species-specific fashion and should be considered organism and population dynamics in specific stressotopes) will when defining a stressotope. Here we discuss the effects of be desirable to describe the effects of stressors. environmental stressors from a dual perspective, including Besides cortisol, other mediators of stress responses, the physical heterogeneity (natural and man-made) and the namely major regulatory axis components (ACTH, CRH, reeducation of genomic landscapes in populations placed under proopiomelanocortin –POMC- peptides, β-endorphin, α- explicitly perceived predation risk. MSH), opioids and a myriad of immune cytokines have been The term “fishes” continue to be a phylogenetic trap that extensively used to define commonalities in altered stress encompass a loosely grouping of more than 28,600 species of states, but the species bias remain. In the last decade the quest ray-finned fish (Actinopterygii) and elasmobranchs, unequally for commonalities of stress responses in fish has focused in distributed in freshwater (12,740 species) and marine (15,886 peripheral structures such as the mucosae, that sense and species) environments (33). The distribution and diversity of life distribute alarm signals from pathogens, parasites, bacteria, story patterns in extant fish reflect the differential characteristics injuries, sudden changes of salinity or oxygen or the presence of both realms that helped to shape the organization and of chemicals in the water (20, 21). Skin, gills or intestine may expression of stress-related genome structures. Teleosts comprise often be the first structures that sense the stressors, but they a monophyletic group that accounts for roughly 98% of species do so again in a marked species-specify manner (20, 22, 23). of ray-finned fishes. Both marine and freshwater environments The reorganization of the overall metabolism to cope with the seem to be dominated by percomorphs and ostariophysians stressors also involve an alteration of thyroidal axis (24) related to (34), but marine fishes show an unexplained low diversity in the energetics and mobilization of fat resources, especially in fish a realm that covers 70% of the Earth’s surface (35). Several undergoing severe metamorphosis regulated by environmental competing hypothesis have been suggested unsuccessfully to shortages, such as in smolting salmons (25, 26). Under stress, explain such differences, ranging from ecological constrictions, growth is arrested, the reproductive processes are suppressed or homogeneity-heterogeneity of water biotopes or ocean’s net depressed and chronic stressors induce immune suppression, in primary productivity and spatial heterogeneity [see (34–36) particular in expensive processes such as white cell production for a comprehensive review]. Freshwater fishes inhabit a and antibody production, whereas other responses such as 0.01% of available planetary water volume, usually more phagocytosis may be maintained (27, 28). However, as seen in fragmented, prone to isolation and barred to dispersal of whole organism physiological responses, at the cellular level organisms than oceanic environments (37). This favors intense the delicate equilibrium between adaptive and maladaptive selective pressures that quite frequently lead to niche-specific stress seems to be the norm. Reactive oxygen species (ROS), for diversification, adaptive radiations and increasing speciation, example, signal oxidative stress as an evolutionary conserved the many phenotypes of African cichlids being the most cited phagocyte response to infection or xenobiotics (29). However, example of such processes (38). It has also been described a as part of the environmental stress response, the expression of greater resilience to extinction in these freshwater low-density, ROS-related genes vary in hermetic fashion: mild oxidative stress high-diversity specialized fish populations compared to their Frontiers in Endocrinology | www.frontiersin.org 4 February 2019 | Volume 10 | Article 62 Balasch and Tort Netting the Stress Responses in Fish marine counterparts (39), probably due to the differential common stress phenotypes expressed from stress-related genetic exploitation of resources (detritivores seem to be more markers may quickly reverse in a population-specific manner, abundant in freshwater environments) and large-scale geological hindering the definition of a set of common stress genes. perturbations. In this sense, freshwater taxa seem to be more Moreover, the expression of gene regulatory networks observed affected and selected for temperature and climatic variations in different populations of killifish was complex enough to (33). preclude a one-to-one relationship between clusters of expressed Anoxia and osmotic changes affect teleost performance, but, genes and adaptive features of observed fish phenotypes (50), being fish ectothermic and oxygen levels and saline content probably due to the heterogeneity of xenobiotic stressors. Even strongly dependent of temperature, thermal conditions largely so, under strong selective pressures, convergent evolution may define the boundaries of stressotopes. In fish, a sudden drop favor the expression of a handful of stress-induced genes (51, 52), in temperature diminishes the production of immune cellular shared among populations and, possibly, species. This may and molecular resources, impairs T cell-dependent immune be useful for the purposes of establishing a common set of responses and may led to cellular inactivation or anergy (40–42). pan-specific responses to different stressors in fish. High temperatures correlate with enhanced parasite transmission The effects of chronic stressors are context-dependent and resilience within hosts’ bodies (43, 44), even when the onset and involve a long-term activation of HPI, SC, and of behavioral fever may stimulate phagocytic activation and other physiological axis (reproductive, immunological, modulate innate humoral responses (45). In fish, shifting too thyroidal/metabolic) influenced by stress. In the quest for far away from thermopreferendum wakes up distress-induced rationalize and simplify stress responses across species, an genes and alters the responsiveness of HPI and immune axis even more applied definition of stress may help (53): perceived (46), but the overall effect may be modulated by acclimation anticipatory stress, acute or not, resulting from continuous to temperature changes (42). In this sense, the plasticity of predation risk. Laundré’s “Landscape of Fear” (LoF) defines this phenotypic responses to thermic-related stressors dictates the perceived stress considering the risks of foraging in unsafety type and relevance of physiologic variables to be included in a habitats (54). Predation risk, parasite load, metabolic trade-offs stressotope. associated to seasonal resource shortages, living in high density From those observations it is clear that the number and populations, or artificial habitats, HIREC influences and evolved distribution of fish species and, consequently, their physiological life story traits have been used to frame the stress related to a strategies to cope with stress result from, and are influenced particular biotope, usually measuring behavioral patterns and by the different rates of speciation and extinction (i.e., net glucocorticoid levels as distress indicators (55, 56). However, diversification) in each environment. Several model species, despite the content-rich description of these analyses, few such as trout, zebrafish or carps inhabit freshwater niches studies have approached the effects of LoF in fish. Behavioral and may endure unexpected selective pressures due to the cascades and patterns of risk aversion have been documented limitations of toxic drainages, xenobiotic clearance or dissolved in coral reef fishes (57–59) and juvenile salmonids (60). In a oxygen-consuming autotrophic blooms, common to lentic highly simplified model of predator-prey relationship between environments. Under these conditions a high turnover of species trout (Oncorhynchus. mykiss) and its prey, (Daphnia pulex) richness, together with accelerated evolution of stress-related in a salinized environment coupled with alarm kairomones, homeostatic mechanisms is to be expected. For example, osmotic stress diminished the predatory pressure and favored in fast-growing short-lived killifish species, the exposome, prey abundance, whereas alarm cues reduced trout aggression defined as an adding-up response to a lifetime expositions to (61). The effects of combined stressors, however, did not affect environmental insults (47) correlates with a fast paced adaptation trout growth, probably due to the limitations of the model. to Human Induced Rapid Environmental Changes, HIREC (48). The individual’s perception of stress may also collide with Complexity, severity and pace of HIREC changes have been the maladaptive effects of HIREC-related ecological traps. Albeit proposed to explain the rapidly acquired tolerance to stress scarcely studied in fish, man-made changes in an otherwise of different populations of killifish (Fundulus heteroclitus) in low-quality habitat may attract fishes unable to properly evaluate polluted estuaries (49). In this species, a maladaptive stress the amount of resources available. As a result, a behavioral glitch scenario forced the emergence of genetic polymorphisms related may lead to a struggle to survive in an “evolutionary trap” (62). to xenobiotic clearance and stress responses such as the aryl For example, drifting fish aggregation devices act as supernormal hydrocarbon receptor (ahr) signaling pathways, cytochrome stimuli (63) and may lure tuna species to misinterpret habitat P450 1A (cyp1a), heat shock proteins (hsp70), multidrug resources (64); coho salmon (O. kisutch) prefer spawning habitats resistance transport proteins (mrp) and estrogen receptors that greatly reduce their survival (65); and increased water (esr2b). In this model of distress modulation, the environmental acidification confounds visual cues in damselfish (Pomacentrus trade-offs defined a pattern of gene expression and the emergence amboinensis) reducing their antipredator responses (66). of low-responders stress-tolerant populations, but the fitness Taken together, those studies confirm not only that the costs depended on specific particularities of newly adapted complexity of the stressotope should be assessed against a phenotypes. This suggests that the physiological costs of evolving minimum common number of informative variables (Figure 2), tolerances to specific stressors strongly depend on the population not restricted to binary food webs, but also the relevance of and individual fitness in a particular niche. In other words, ecophysiological approaches to describe a unified response in diversified population assemblages, well-characterized and to stress in teleosts. Both net diversification and the effects Frontiers in Endocrinology | www.frontiersin.org 5 February 2019 | Volume 10 | Article 62 Balasch and Tort Netting the Stress Responses in Fish thoroughly reviewed elsewhere (67–70). Dissecting genome- based responses to severe stressors implies an extensive analysis of gene regulatory networks and interactions in cellular and tissue environments. To make the analysis of genome-phenome interactions more manageable, we can define a “stressome,” or catalog of genes and its products expressed when the organism suffers a maladaptive stress, a concept borrowed from studies of microbial resistance to stressful insults (71) that has been coined to characterize the roadmap to stress-related changes in genomic, proteomic, and metabolomic arenas (72, 73). Stressomes pave the way to a precise definition of stressotopes, but several methodological and conceptual issues have arisen in the course of the genocentric turn of fish stress physiology, mainly the scarcity of model species and the peculiarities of fish genomes that affect their expression, plasticity and evolvability under maladaptive scenarios. Several species of teleosts are considered the gold standard for developmental, evo-devo, stress-related, and toxicogenomic studies (20, 74–80). However, to date <0.5% of those species have a detailed, but still far from being systematic, coverage of genomic data (81). From the vantage point of comparative studies, teleost genomes differ from those of other vertebrates in terms of divergence and redundancy. In addition to the two events of whole genome duplication common to early vertebrates, teleost endured another round of teleost-specific FIGURE 2 | A non-exhaustive list of stressotope components. In fish, the fate of stress responses to natural (temperature and oxygen variations, changes in genome duplication 320 million years ago (Mya) (82). Some salinity and photoperiod, abundance of pathogens in freshwater and marine lineages widely used as model species, such as Salmonidae realms...), artificial (cultured) and Human Induced Rapid Environmental and Cypriniformes have experienced yet another process of Changes (HIREC) depends mainly, but not only, on environmental insults, tetraploidization, ∼80 and 8 Mya, respectively (83, 84). To what perceived stressful scenarios influenced by continuous predation risk extent this diversification leads per se to increased phenotypic (Landscape of Fear, LoF) and species-specific intersex differential activation of stress, immune and metabolic axes. To what extent phenotypic plasticity helps plasticity and adaptability to environmental stressors by means to cope with maladaptive stressors in turn depends on evolutionary conserved of neofuncionalization of duplicated genes is still controversial life stories and behavioral repertoires (see the text for details and (85, 86), being the subfuncionalization (the functional division abbreviations). of ancestral genes among the duplicated ones), loss of genes or slow evolution of duplicate genes three major outcomes of genome duplication (87, 88). For example, the recent (<10 Mya) of perceived risk of depredation and foraging in natural and independent evolution of anadromy in salmonid clades has been artificial habitats provide a coarse-grained description of correlated to cooler temperatures that opened new estuarine and environmentally-related impacts on stress physiology in teleosts freshwater habitats, and also redefined previous stressotopes, and may help to discriminate shared mechanisms common to favoring speciation (85). As described for extremely diversified stress responses in fish, but the historical genomic remodeling non-tetraploid cichlids, several ecophysiological factors may must also be considered. influence a successful radiation to stressful environments without specific genome duplications. Instead, genome-wide ROLLING GENOMES diversifying selection on key genes, gene duplication and regulation by microRNAs and transposable elements may have To delineate a stressotope, a set of pan-specific genes involved allowed their adaptive radiation (89). Additionally, the teleost in maladaptive responses to stress must be defined. In the genomes analyzed to date seem to have suffered accelerated seascape of fish phenomes, genomes are being continuously rates of nucleotide divergence, high rate of intron turnover tested and polished against the evolutionary coupling between and dramatic loss of conserved noncoding sequences and cis- environmental and endogenous selective pressures. This regulatory elements [see (90) for a comprehensive review] that affects specifically the recent omics interpretations of may contribute to their great phenotypic diversity in response to adaptive physiology of stress in fish. In less than a decade, stressful ever-changing environments. However, this may impair stress studies have evolved from moleculocentric analysis to the inclusion of a set of common stress-related genes as required genocentric approaches, and lately, to genome-wide association when defining a stressotope. studies, proteomic analysis and high throughput genomic This implies that the species-specificity biases the comparative interpretations of genetic and epigenetic networks’ cross-talking genomics of teleosts, but a stressome made of a set of common with environmentally-induced phenotypes that have been predictors of distress still can be assembled from genome-wide Frontiers in Endocrinology | www.frontiersin.org 6 February 2019 | Volume 10 | Article 62 Balasch and Tort Netting the Stress Responses in Fish analysis. This is the case for annual killifish genomes that contain Teleost inhabit a stress-prone scenario that favors the several hsp transcripts and genes associated with mitochondrial evolution of highly reactive immunological surfaces, such function that confer resistance to severe (and more importantly, as fish mucosal skin, gills, or gut, infiltrated by mucosa- predictable) environmental anoxia stress during development associated lymphoid tissues (MALT), exquisitely sensitive and diapausa stages (91). Atlantic cod (Gadus morhua) also to pathogenic or xenobiotic insults (21), and that’s why the has a surprisingly high number of major histocompatibility analysis of interfacial tissues can be so rewarding to define a complex (MHC) I genes that supply the absence of MHC II stressome. Fish skin scaffolding consists of a highly secretory components, thus maintaining functional antigen trapping and non-queratinized living tissue that harbors stress-sensing processing pathways during the onset of immune responses cells, skin associated lymphoid tissues (SALT) packed with B (92, 93) in microbial-rich environments. Despite their disparate and T cells, resident or errand myeloid phagocytes and cells life stories, metabolism, longevity and genome scaffolding, both that produce microbicidal molecules and protective mucus. species can still act as genomic models and source of candidate Teleost SALT induce and regulate local adaptive immune predictors for distress-related markers because the processes responses that may communicate with other mucosal tissues evaluated (the extreme stress tolerance and the alternate antigen (branchial, GIALT, and intestinal, GALT) and influence processing) recruit enough identical or very similar categories of the immune reactivity of systemic lymphoid (head kidney, predictors for an effective description of a common stressome. spleen, thymus) and metabolic (liver) organs. In addition Gene expression profile outcomes may differ between stressors to immunological sensing and regulation, fish gills and gut and species, and the methodology is certainly not without pitfalls are also involved in osmoexcretory/acid-base balance and [see (94, 95) for a detailed discussion], but including the adaptive energetic metabolism (105, 106). In fish, such multipurpose life stories and the environmental biotope may normalize the organs serve both as probes to distressful environmental analysis of physiological responses to distress. For instance, changes and as effectors of allostatic rearrangements of uncovering the seasonal oscillations of stress-related regulatory stress-related hormonal axis, and may be specially suited networks may help to define stressotopes in a more realistic way. to define minimum common molecular markers of distress Cortisol has been shown to induce the expression of per1a and across species. In a recent study (20), the short-term effects per1b and repress bma11a and clock genes that control circadian of hypoxia and vaccination against Vibrio anguillarum rhythms in fish, and it has been proposed to act as a modulator elicited a strongly interspecific differential response of pro- of molecular oscillators (19, 96). Molecular clocks that respond inflammatory and stress-related genes in MALT of gilthead to environmental factors such as light and dark cycles, food seabream (Sparus aurata), a marine species, and rainbow trout availability and thermal conditions vary both in natural and (Oncorhynchus mykiss), a freshwater teleost, being the former in HIREC environments and may contribute to the ticking of more responsive to stressors. The stress- and immune-related stressomes in a set of defined stressotopes involving migration transcripts tested (lysozyme, c3, igm, hsp70, cox2, Il1β, tnfα, and breeding scenarios (97). il6, il10, and tgfβ1), together with the analysis of mucosal- Epigenetic modification of xenobiotic and temperature and plasmatic-derived cortisol levels constitute a typical set stress-related gene expression should also be considered to of markers of distressed states that may help to define a define a teleost stressome. Fish genomes differ from those of minimum common set of gene-driven responses to stressors mammals in the number of methylated sites retained early in teleosts. in development and contain exclusive DNA methyltransferase genes that may help in the vertical transmission of the epigenome (98, 99), but the overall modulation of gene expression follows JANIAN PHENOMES the vertebrate pattern (100). Epigenetic analyses have been used to test the effects of captive rearing in salmons, suggesting that Nested in the archaic roman pantheon, a two-headed figure, hatchery-induced epigenetic changes impair the osmoregulatory Janus, represent, among other things, the transition from one seawater acclimation and swimming performance during state to another, or from the past to the future. In both vertebrates smoltification (101). In zebrafish (Danio rerio), xenobiotic and invertebrates, behavioral phenotypes may change during the exposure modified methylation patterns during embryogenesis lifetime of an individual, following a reaction norm defined by (102). Diversification of cortisol-responder phenotypes in environmental changes that enhance or suppress the expression stickleback (Gasterosteus aculeatus) offspring of stressed mothers of key behavioral mediators, and constrained by the adaptability has been ascribed also to epigenetic changes (103) signaled by of the genome (107). A stressotope should consequently be glucocorticoid receptors. Little is known about the long-term defined by the ontogenic variations and changing phenotypes effects of vertical transmission of stressed phenotypes in fish, but that the organism endure in diverse environments. In teleosts, higher responses to cortisol may reduce the fitness of hatchlings the study of relevant stressful-prone “janian” phenotypes has and contribute to allostatic load in stressful environments (104). come to focus in recent years in the grounds of fish welfare, and In addition, adaptive epigenetic modifications of gene expression include among others the ecological distribution of differentiated strongly depend upon the degree, intensity and predictability behavioral syndromes or individualities (“personalities”) ruled of environmental changes that may propitiate maladaptive by environmental stressors [extensively reviewed in (108) and outcomes of epigenetic modifications, such as the epigenetic not to be discussed here], the pathogen effects on physiological traps discussed below. modifications underlying sequential sex changes and the Frontiers in Endocrinology | www.frontiersin.org 7 February 2019 | Volume 10 | Article 62 Balasch and Tort Netting the Stress Responses in Fish physiological changes linked to transition from freshwater to sticklebacks (Gasterosteus aculeatus) and the cestode parasite marine realms in diadromous species. Schistocephalus solidus (123). When exposed to high doses of The majority of fish follow the usual vertebrate gonochorism, estradiol, parasitized stickleback males were found to be greatly with both sexes being determined genetically or environmentally affected, more than females by parasite growth. (109). Several teleosts also indulge in a plethora of rare vertebrate A reduction of fitness in one sex has also been suggested reproductive modes ranging from simultaneous and sequential as the trigger of selective vulnerabilities in species with hermaphroditism to parthenogenesis (110, 111) that have been environmentally-directed sex determination (ESD). Unexpected ascribed to differential ecological selective pressures (111), temperature changes may influence epigenetic regulation diversification of reproductive mediators by means of whole of breeding strategies in teleosts with ESD as described for genome duplication events (86) and fish-specific idiosyncrasies mangrove killifishes (124). Similar to the “ecological traps” of gonadal axis. Males and females usually inhabit the same discussed above, severe environmental or HIREC variations environment, but the selective pressures faced by both sexes could skew the sex ratio by inducing short term epigenetic may differ owing to variations in size, competition for resources, changes that favor accelerated adaptation to novel environments diet, microhabitat use aggressiveness and metabolic trade-offs but can become “epigenetic traps” in the long term, benefiting between gamete production/fecundity and immune resistance to one sex and decreasing the fitness of the other (125). The same parasitic load (112), even in sex-role-reversed species (113). holds true for sequential hermaphroditic species (126), such as Several sex-biased effects of parasitism and facultative the extensively farmed Sparidae. Several species of this family infections have been described in natural and artificial practice protandrous (changing sex from males to females) populations of teleosts. Poeciliids have been used as a model to and protogynous (the opposite) hermaphroditism (127). In highlight the relevance of sex-specific evolution of physiological protandrous gilthead sea bream (Sparus aurata) populations, responses to environmental changes on a macroevolutioanry the few large fertile females surrounded by many smaller males basis (114). Polygynous guppies (Poecilia reticulata) parasitized skew the sex ratio and have greater fitness measured by the by Gyrodactylus spp., showed an increased responsiveness number of offspring (128). In this species, reproductive success to infection in females that lead to differential evolution of may be linked to the high rates of evolution of female-biased resistance phenotypes (115). Male guppies also differ from genes compared to male-biased genes (129), probably due to females in the navigational abilities associated to increased differential selective pressures for both sexes at each stage. This dispersion and mobility in complex environments (116) and suggests that the effect of environmental stressors may affect the seems to be more prone to parasite infection than females (117). sex-biased expression of genes in hermaphrodites in a different Unpredictable chronic stress (social isolation, crowding, tank way from what has been described in gonochoristic teleosts. changes, thermal variations, and chasing) affect zebrafish males In diadromous species, the still poorly understood and but not females (118), highlighting the double effect of species- complex influence of glucocorticoids as mediators of stress specificity and sex-biased covariation in stress studies. The responses modulates stressome structure and function. In offspring of largemouth bass females (Micropterus salmoides) teleosts, crossing continental and oceanic aquatic environments treated with cortisol showed lower responsiveness to stress and stresses the physiology of osmoregulation and metabolism in a exhibit less exploratory behavior and aggression than those of complex combination of enhancing and suppressive expression non-treated females (119), adding to the stressotope equation the of HPI, growth and thyroidal axes. A recent study embraced the still imprecisely described mechanism of vertical transmission of joint analysis of ontogenetic stages, sexual, and parasitic effects stress-related phenotypes. in hypoxia-stressed European eels (Anguilla anguilla), defining Parasitic load and unexpected environmental changes may a limited stressotope to modulate the causes and consequences also contribute to the stressful effects of sex-biased physiologies. of the stepped decline in eel populations (130). Parasitized eels Parasite burden accounts for a large portion of stressors in showed stronger levels of plasmatic cortisol and higher gill aquatic habitats, and in vertebrates immunocompetence depends Na+/K+—ATPase activity that added up to physical constraints largely on male and female sex hormones, being testosterone (salinity, temperature) to mark female eels in the last stage of generally immunosuppresive and estrogens enhancers of silvering to be more prone to be stressed by the combined effects immune system in a broad sense (120). Vertebrate males also of several stressors. The synergistic effects of parasitism, hypoxia tend to rely more than females in Th1-mediated immune and biotic factors included in the analysis of eel physiology signal responses (linked to defensive responses against intracellular the way by which a comprehensive and realistic study of stress bacterial and viral parasites) whereas females display generally responses should be performed. In anadromous salmonids, for higher Th2-mediated extracellular responses against parasites instance, long-lasting migrations subdue the cortisol resistance (121). Both T-cell related immune responses have been described and chronically stress semelparous species. To date, the crosstalk in fish, albeit with species-specific kinetics that may interfere between immune and hormonal components remains unsolvable or potentiate with the resistance to severe infection (122) due to the complexity of the activation/suppression interplay and the intensity of distress responses. However, sex-specific between cortisol, thyroid, growth and sex hormones, B cell responses to reproductive hormones may be altered by HIREC lymphopoiesis, inflammation, antibody responses and the changes in water composition, as demonstrated by the effects of development of immunological memory at different stages endocrine disrupting chemicals such as 17β-oestradiol in host- of their life cycle (131). In this case, the stressotope demands pathogen interaction between males and females of three-spined a pronounced level of multiscale complexity to integrate the Frontiers in Endocrinology | www.frontiersin.org 8 February 2019 | Volume 10 | Article 62 Balasch and Tort Netting the Stress Responses in Fish adaptive vs. maladaptive effects of stress in such migratory of fish lifestyles to a minimum common set of telltales and species. indicators of allostatic loads originating from multiple and As discussed above, fish stressotopes harbor several recurrent stressors. There is a growing shift in the literature of opportunistic and obligate parasitic, fungal, viral, and bacterial stress responses in fish toward a more integrate view of allostatic pathogens that may transmit stress-prone phenotypes vertically, description. However, this approach is still hampered by the lack by parasite colonization of gonadal tissues, and direct cortisol of analytical tools, peculiarities of fish genomes and the fuzzy effects into eggs (119, 132) and affect not only broodstock definition of common inter-specific endpoints of distress-related and natural populations but both sexes differentially as well. physiological changes across behavioral phenotypes. Moreover, Therefore, the puzzling diversity of teleost reproductive strategies fish are considered more labile and diverse in their physiology may be also partially explained assuming compensatory genetic than other vertebrates. We can describe teleosts as animals changes that overcome maladaptive responses to distressful that indulge in sex changes, inhabit environments hostile environments. This leads to plastic reproductive adaptations to ectothermic metabolisms, grow indefinitely, modify their between sexes to predatory and pathogenic pressures by virtue of coping styles, or individualities in response to environmental sex-specific differences in the reproductive hormonal axis. and parasitic insults (135, 136), have higher rates of cell Overall, these and other studies imply that to accurately proliferation in the adult brain compared to mammals, and that define a stressotope, the range of abnormal values in distress are strongly dependent on the social interactions and physical physiological adjustments, the scope of stressome components environments (137, 138). Therefore, a roadmap for minimum to be included in the analysis of allostatic load and the intersex common descriptors of stress responses, a stressotope, must differential responses to severe stressors, should necessarily be be drawn considering the behavioral plasticity of teleosts, an taken into account. Considering that in teleosts, as in the rest integrative concept that harbors the cross-linked effects of of vertebrates, steroids regulate reproductive outcomes but also neuroimmunoendocrine cross-talks that integrate in a variable metabolism, stress responses, behavior and immune function, set of phenotypes from specific activation of pan-specific usually in a seasonal way (133, 134), the differential effect of stressomes. estrogens- and testosterone-derived mediators must be included in the stressome catalog. AUTHOR CONTRIBUTIONS CONCLUSION JB and LT conceived and wrote the review and JB crafted the figures. Both authors contributed to manuscript revision, read, We have outlined some of the key processes and influences and approved the submitted version. required to properly define a stressotope, ranging from the molecular to the ecological ones. Stress is a foreground concept ACKNOWLEDGMENTS defined against a background of interactions between network genome expression and phenome consolidation in a particular JB and LT are members of the network Healthiest fish, devoted ecological niche. A stressotope approach that could help to to the study of stress and welfare in fish (supported by MICINN elucidate common responses to diverse stressful scenarios is MINECO-AGL2016-81808-REDT, Spanish Government and not only informative but also necessary to reduce the diversity EU-FEDER funds). REFERENCES dose-response framework. Toxicol Appl Pharmacol. (2007) 222:122–8. doi: 10.1016/j.taap.2007.02.015 1. Roberts RJ. Fish Pathology. Oxford: John Wiley & Sons (2012). 10. Sterling P. Allostasis: a new paradigm to explain arousal pathology. Handb 2. Semple SL, Vo NTK, Li AR, Pham PH, Bols NC, Dixon B. Development and Life Stress Cogn Health (1988) 629–49. use of an Arctic charr cell line to study antiviral responses at extremely low 11. Wendelaar Bonga SE. The stress response in fish. Physiol Rev. (1997) 77:591– temperatures. J Fish Dis. (2017) 40:1423–39. doi: 10.1111/jfd.12615 625. doi: 10.1152/physrev.1997.77.3.591 3. Lynch MDJ, Neufeld JD. Ecology and exploration of the rare biosphere. Nat 12. Gorissen M, Flik G. The endocrinology of the stress response in fish: an Rev Microbiol. (2015) 13:217–29. doi: 10.1038/nrmicro3400 adaptation-physiological view. In: Schreck CB, Tort L, Farrell A and Brauner 4. Olenin S, Ducrotoy J-P. The concept of biotope in marine C, editors. Fish Physiology. London: Elsevier. p. 75–111. ecology and coastal management. Mar Pollut Bull. (2006) 53:20–9. 13. Pankhurst NW. The endocrinology of stress in fish: an doi: 10.1016/j.marpolbul.2006.01.003 environmental perspective. Gen Comp Endocrinol. (2011) 170:265–75. 5. Schreck CB, Tort L, Farrell A, Brauner C (editors). The concept of stress in doi: 10.1016/j.ygcen.2010.07.017 fish. Fish Physiology. London: Elsevier. p. 1–34. 14. Culbert BM, Gilmour KM. Rapid recovery of the cortisol response following 6. Selye H. The Stress of Life: Rev Ed. Oxford: McGraw-Hill (1978). social subordination in rainbow trout. Physiol Behav. (2016) 164:306–13. 7. Koolhaas JM, Bartolomucci A, Buwalda B, de Boer SF, Flügge G, Korte SM, doi: 10.1016/j.physbeh.2016.06.012 et al. Stress revisited: a critical evaluation of the stress concept. Neurosci 15. Nagrodski A, Murchie KJ, Stamplecoskie KM, Suski CD, Cooke Biobehav Rev. (2011) 35:1291–301. doi: 10.1016/j.neubiorev.2011.02.003 SJ. Effects of an experimental short-term cortisol challenge on the 8. Selye H. Stress without distress. In: Serban G, editor. Psychopathology of behaviour of wild creek chub Semotilus atromaculatus in mesocosm Human Adaptation. Springer. p. 137–46. and stream environments. J Fish Biol. (2013) 82:1138–58. doi: 10.1111/jfb 9. Calabrese EJ, Bachmann KA, Bailer AJ, Bolger PM, Borak J, Cai L, .12049 et al. Biological stress response terminology: integrating the concepts 16. Pleizier N, Wilson ADM, Shultz AD, Cooke SJ. Puffed and bothered: of adaptive response and preconditioning stress within a hormetic personality, performance, and the effects of stress on checkered Frontiers in Endocrinology | www.frontiersin.org 9 February 2019 | Volume 10 | Article 62 Balasch and Tort Netting the Stress Responses in Fish pufferfish. Physiol Behav (2015) 152:68–78. doi: 10.1016/j.physbeh.2015. 42. Dietrich MA, Hliwa P, Adamek M, Steinhagen D, Karol H, Ciereszko A. 09.011 Acclimation to cold and warm temperatures is associated with differential 17. Pottinger TG, Pickering AD, Hurley MA. Consistency in the stress response expression of male carp blood proteins involved in acute phase and stress of individuals of two strains of rainbow trout, Oncorhynchus mykiss. responses, and lipid metabolism. Fish Shellfish Immunol. (2018) 76:305–15. Aquaculture (1992) 103:275–89. doi: 10.1016/0044-8486(92)90172-H doi: 10.1016/j.fsi.2018.03.018 18. Ellis T, Yildiz HY, López-Olmeda J, Spedicato MT, Tort L, Øverli Ø, 43. Żbikowska E., Cichy A. Can Parasites Change Thermal Preferences of et al. Cortisol and finfish welfare. Fish Physiol Biochem. (2012) 38:163–88. Hosts?. In: Mehlhorn H, editor. Host Manipulations by Parasites and Viruses. doi: 10.1007/s10695-011-9568-y Parasitology Research Monographs, vol 7. Cham: Springer (2015). 19. Isorna E, de Pedro N, Valenciano AI, Alonso-Gómez ÁL, Delgado 44. Franke F, Armitage SAO, Kutzer MAM, Kurtz J, Scharsack JP. MJ. Interplay between the endocrine and circadian systems in fishes. J Environmental temperature variation influences fitness trade-offs and Endocrinol. (2017) 232:R141–59. doi: 10.1530/JOE-16-0330 tolerance in a fish-tapeworm association. Parasit Vectors (2017) 10:252. 20. Khansari AR, Balasch JC, Vallejos-Vidal E, Parra D, Reyes-López FE, Tort L. doi: 10.1186/s13071-017-2192-7 Comparative immune- and stress-related transcript response induced by air 45. Boltana S, Aguilar A, Sanhueza N, Donoso A, Mercado L, Imarai M, exposure and Vibrio anguillarum bacterin in rainbow trout (Oncorhynchus et al. Behavioral fever drives epigenetic modulation of the immune mykiss) and Gilthead Seabream (Sparus aurata) Mucosal Surfaces. Front response in fish. Front Immunol. (2018) 9:1241. doi: 10.3389/fimmu.2018 Immunol. (2018) 9:856. doi: 10.3389/fimmu.2018.00856 .01241 21. Salinas I. The mucosal immune system of teleost fish. Biology (2015) 4:525– 46. Mateus AP, Costa RA, Cardoso JCR, Andree KB, Estévez A, Gisbert 39. doi: 10.3390/biology4030525 E, et al. Thermal imprinting modifies adult stress and innate immune 22. Parra D, Reyes-Lopez FE, Tort L. Mucosal immunity and B Cells in responsiveness in the teleost sea bream. J Endocrinol (2017) 233:381–94. teleosts: effect of vaccination and stress. Front Immunol. (2015) 6:354. doi: 10.1530/JOE-16-0610 doi: 10.3389/fimmu.2015.00354 47. Wild CP. Complementing the genome with an “exposome”: the 23. Rosengren M, Thörnqvist P-O, Winberg S, Sundell K. The brain-gut axis outstanding challenge of environmental exposure measurement in of fish: Rainbow trout with low and high cortisol response show innate molecular epidemiology. Cancer Epidemiol Biomark Prev Publ Am differences in intestinal integrity and brain gene expression. Gen Comp Assoc Cancer Res Cosponsored Am Soc Prev Oncol. (2005) 14:1847–50. Endocrinol. (2018) 257:235–45. doi: 10.1016/j.ygcen.2017.09.020 doi: 10.1158/1055-9965.EPI-05-0456 24. Peter MCS. The role of thyroid hormones in stress response of fish. Gen 48. Sih A, Trimmer PC, Ehlman SM. A conceptual framework for understanding Comp Endocrinol. (2011) 172:198–210. doi: 10.1016/j.ygcen.2011.02.023 behavioral responses to HIREC. Curr Opin Behav Sci. (2016) 12:109–14. 25. Geven EJW, Klaren PHM. The teleost head kidney: Integrating doi: 10.1016/j.cobeha.2016.09.014 thyroid and immune signalling. Dev Comp Immunol. (2017) 66:73–83. 49. Whitehead A, Clark BW, Reid NM, Hahn ME, Nacci D. When evolution is doi: 10.1016/j.dci.2016.06.025 the solution to pollution: Key principles, and lessons from rapid repeated 26. Holzer G, Laudet V. Thyroid hormones: a triple-edged sword for life history adaptation of killifish (Fundulus heteroclitus) populations. Evol Appl. (2017) transitions. Curr Biol CB (2015) 25:R344–7. doi: 10.1016/j.cub.2015.02.026 10:762–83. doi: 10.1111/eva.12470 27. Tort L. Stress and immune modulation in fish. Dev Comp Immunol. (2011) 50. Whitehead A, Galvez F, Zhang S, Williams LM, Oleksiak MF. Functional 35:1366–75. doi: 10.1016/j.dci.2011.07.002 genomics of physiological plasticity and local adaptation in killifish. J Hered. 28. Yada T, Tort L. Stress and disease resistance: immune system and (2011) 102:499–511. doi: 10.1093/jhered/esq077 immunoendocrine interactions. In: Schreck CB, Tort L, Farrell A and 51. Lindsey HA, Gallie J, Taylor S, Kerr B. Evolutionary rescue from extinction Brauner C, editors. Fish Physiology. London: Elsevier. p. 365–403. is contingent on a lower rate of environmental change. Nature (2013) 29. Lushchak VI. Contaminant-induced oxidative stress in fish: a 494:463–7. doi: 10.1038/nature11879 mechanistic approach. Fish Physiol Biochem. (2016) 42:711–47. 52. Fisher MA, Oleksiak MF. Convergence and divergence in gene expression doi: 10.1007/s10695-015-0171-5 among natural populations exposed to pollution. BMC Genomics (2007) 30. Niki E. Oxidative stress and antioxidants: distress or eustress? Arch Biochem 8:108. doi: 10.1186/1471-2164-8-108 Biophys. (2016) 595:19–24. doi: 10.1016/j.abb.2015.11.017 53. Boonstra R. Reality as the leading cause of stress: rethinking the 31. de Nadal E, Ammerer G, Posas F. Controlling gene expression in response to impact of chronic stress in nature. Funct Ecol. (2013) 27:11–23. stress. Nat Rev Genet. (2011) 12:833–45. doi: 10.1038/nrg3055 doi: 10.1111/1365-2435.12008 32. Dhabhar FS. Effects of stress on immune function: the good, the bad, and the 54. Laundré JW, Hernández L, Medina PL, Campanella A, López-Portillo J, beautiful. Immunol Res. (2014) 58:193–210. doi: 10.1007/s12026-014-8517-0 González-Romero A, et al. The landscape of fear: the missing link to 33. Guinot G, Cavin L. Contrasting “Fish” diversity dynamics between understand top-down and bottom-up controls of prey abundance? Ecology marine and freshwater environments. Curr Biol. CB (2015) 25:2314–8. (2014) 95:1141–52. doi: 10.1890/13-1083.1 doi: 10.1016/j.cub.2015.07.033 55. Gallagher AJ, Creel S, Wilson RP, Cooke SJ. Energy landscapes 34. Carrete Vega G, Wiens JJ. Why are there so few fish in the sea? Proc Biol Sci. and the landscape of fear. Trends Ecol Evol. (2017) 32:88–96. (2012) 279:2323–9. doi: 10.1098/rspb.2012.0075 doi: 10.1016/j.tree.2016.10.010 35. May RM. Biological diversity: differences between land and sea. Phil Trans R 56. Lawrence MJ, Eliason EJ, Brownscombe JW, Gilmour KM, Mandelman Soc Lond B (1994) 343:105–11. doi: 10.1098/rstb.1994.0014 JW, Cooke SJ. An experimental evaluation of the role of the stress 36. Vermeij GJ, Grosberg RK. The great divergence: when did diversity axis in mediating predator-prey interactions in wild marine fish. on land exceed that in the sea? Integr Comp Biol. (2010) 50:675–82. Comp Biochem Physiol A Mol Integr Physiol. (2017) 207:21–9. doi: 10.1093/icb/icq078 doi: 10.1016/j.cbpa.2017.02.001 37. Shiklomanov IA. Appraisal and assessment of world water resources. Water 57. Madin EMP, Madin JS, Booth DJ. Landscape of fear visible from space. Sci Int. (2000) 25:11–32. doi: 10.1080/02508060008686794 Rep. (2011) 1:14. doi: 10.1038/srep00014 38. Salzburger W. Understanding explosive diversification through cichlid fish 58. Gil MA, Zill J, Ponciano JM. Context-dependent landscape of fear: algal genomics. Nat Rev Genet. (2018) 19:705–17. doi: 10.1038/s41576-018-0043-9 density elicits risky herbivory in a coral reef. Ecology (2017) 98:534–44. 39. Guinot G, Cavin L. “Fish” (Actinopterygii and Elasmobranchii) doi: 10.1002/ecy.1668 diversification patterns through deep time. Biol Rev. (2016) 91:950–81. 59. Fong CR, Frias M, Goody N, Bittick SJ, Clausing RJ, Fong P. Empirical doi: 10.1111/brv.12203 data demonstrates risk-tradeoffs between landscapes for herbivorous 40. Abram QH, Dixon B, Katzenback BA. Impacts of low temperature on the fish may promote reef resilience. Mar Environ Res. (2018) 133:1–5. teleost immune system. Biology (2017) 6: E39. doi: 10.3390/biology6040039 doi: 10.1016/j.marenvres.2017.11.001 41. Makrinos DL, Bowden TJ. Natural environmental impacts on 60. Harvey BC, White JL. Axes of fear for stream fish: water depth teleost immune function. Fish Shellfish Immunol. (2016) 53:50–7. and distance to cover. Environ Biol Fishes (2017) 100:565–73. doi: 10.1016/j.fsi.2016.03.008 doi: 10.1007/s10641-017-0585-2 Frontiers in Endocrinology | www.frontiersin.org 10 February 2019 | Volume 10 | Article 62 Balasch and Tort Netting the Stress Responses in Fish 61. Hintz WD, Relyea RA. A salty landscape of fear: responses of fish and 82. Taylor JS, Braasch I, Frickey T, Meyer A, Van de Peer Y. Genome duplication, zooplankton to freshwater salinization and predatory stress. Oecologia (2017) a trait shared by 22000 species of ray-finned fish. Genome Res. (2003) 185:147–56. doi: 10.1007/s00442-017-3925-1 13:382–90. doi: 10.1101/gr.640303 62. Robertson BA, Rehage JS, Sih A. Ecological novelty and the 83. Lien S, Koop BF, Sandve SR, Miller JR, Kent MP, Nome T, et al. The emergence of evolutionary traps. Trends Ecol Evol. (2013) 28:552–60. Atlantic salmon genome provides insights into rediploidization. Nature doi: 10.1016/j.tree.2013.04.004 (2016) 533:200–5. doi: 10.1038/nature17164 63. Tinbergen N. The Study of Instinct. Oxford: Oxford Clarendon Press (1951). 84. Xu P, Zhang X, Wang X, Li J, Liu G, Kuang Y, et al. Genome sequence and 64. Hallier J-P, Gaertner D. Drifting fish aggregation devices could act as an genetic diversity of the common carp, Cyprinus carpio. Nat Genet. (2014) ecological trap for tropical tuna species. Mar Ecol Prog Ser. (2008) 353:255– 46:1212–9. doi: 10.1038/ng.3098 64. doi: 10.3354/meps07180 85. Macqueen DJ, Johnston IA. A well-constrained estimate for the timing 65. Jeffres C, Moyle P. When good fish make bad decisions: coho salmon of the salmonid whole genome duplication reveals major decoupling in an ecological trap. North Am J Fish Manag. (2012) 32:87–92. from species diversification. Proc Biol Sci. (2014) 281:20132881. doi: 10.1080/02755947.2012.661389 doi: 10.1098/rspb.2013.2881 66. Ferrari MCO, McCormick MI, Munday PL, Meekan MG, Dixson 86. Glasauer SM, Neuhauss SC. Whole-genome duplication in teleost fishes and DL, Lönnstedt O, et al. Effects of ocean acidification on visual its evolutionary consequences. Mol Genet Genomics (2014) 289:1045–60. risk assessment in coral reef fishes. Funct Ecol. (2012) 26:553–8. doi: 10.1007/s00438-014-0889-2 doi: 10.1111/j.1365-2435.2011.01951.x 87. Lynch M, Conery JS. The evolutionary fate and consequences of 67. Geng X, Sha J, Liu S, Bao L, Zhang J, Wang R, et al. A genome-wide duplicate genes. Science (2000) 290:1151–5. doi: 10.1126/science.290.54 association study in catfish reveals the presence of functional hubs of related 94.1151 genes within QTLs for columnaris disease resistance. BMC Genomics (2015) 88. Jordan IK, Wolf YI, Koonin EV. Duplicated genes evolve slower than 16:196. doi: 10.1186/s12864-015-1409-4 singletons despite the initial rate increase. BMC Evol Biol. (2004) 4:22. 68. Rey O, Danchin E, Mirouze M, Loot C, Blanchet S. Adaptation to global doi: 10.1186/1471-2148-4-22 change: a transposable element-epigenetics perspective. Trends Ecol Evol. 89. Brawand D, Wagner CE, Li YI, Malinsky M, Keller I, Fan S, et al. The (2016) 31:514–26. doi: 10.1016/j.tree.2016.03.013 genomic substrate for adaptive radiation in African cichlid fish. Nature 69. Prunet P, Øverli Ø, Douxfils J, Bernardini G, Kestemont P, Baron (2014) 513:375–81. doi: 10.1038/nature13726 D. Fish welfare and genomics. Fish Physiol Biochem. (2012) 38:43–60. 90. The Divergent Genomes of Teleosts. Annual Review of Animal Biosciences. doi: 10.1007/s10695-011-9522-z Available online at: https://www.annualreviews.org/doi/10.1146/annurev- 70. Gandar A, Laffaille P, Marty-Gasset N, Viala D, Molette C, Jean S. animal-030117-014821 (Accessed September 21, 2018). Proteome response of fish under multiple stress exposure: Effects of 91. Wagner JT, Singh PP, Romney AL, Riggs CL, Minx P, Woll SC, et al.. The pesticide mixtures and temperature increase. Aquat Toxicol. (2017) 184:61– genome of Austrofundulus limnaeus offers insights into extreme vertebrate 77. doi: 10.1016/j.aquatox.2017.01.004 stress tolerance and embryonic development. BMC Genomics (2018) 19:155. 71. Pané-Farré J, Quin MB, Lewis RJ, Marles-Wright J. Structure and Function doi: 10.1186/s12864-018-4539-7 of the Stressosome Signalling Hub. In: Harris JR and Marles-Wright 92. Star B, Nederbragt AJ, Jentoft S, Grimholt U, Malmstrøm M, Gregers TF, J, editors. Macromolecular Protein Complexes: Structure and Function et al. The genome sequence of Atlantic cod reveals a unique immune system. Subcellular Biochemistry. Cham: Springer International Publishing. p. 1–41. Nature (2011) 477:207–10. doi: 10.1038/nature10342 doi: 10.1007/978-3-319-46503-6_1 93. Malmstrøm M, Jentoft S, Gregers TF, Jakobsen KS. Unraveling the evolution 72. Guo X, He Y, Zhang L, Lelong C, Jouaux A. Immune and stress responses in of the Atlantic cod’s (Gadus morhua L.) alternative immune strategy. PLoS oysters with insights on adaptation. Fish Shellfish Immunol. (2015) 46:107– ONE (2013) 8:e74004. doi: 10.1371/journal.pone.0074004 19. doi: 10.1016/j.fsi.2015.05.018 94. Porcelli D, Butlin RK, Gaston KJ, Joly D, Snook RR. The environmental 73. Privitera M, Floriou-Servou A, Bohacek J. Dissecting genomics of metazoan thermal adaptation. Heredity (2015) 114:502–14. stress with transcriptomics. OncoTarget (2017) 8:10783–4. doi: 10.1038/hdy.2014.119 doi: 10.18632/oncotarget.14693 95. Evans TG. Considerations for the use of transcriptomics in identifying 74. Krishnan J, Rohner N. Cavefish and the basis for eye loss. Philos Trans R Soc the “genes that matter” for environmental adaptation. J Exp Biol. (2015) Lond B Biol Sci. (2017) 372:20150487. doi: 10.1098/rstb.2015.0487 218:1925–35. doi: 10.1242/jeb.114306 75. Khansari AR, Parra D, Reyes-López FE, Tort L. Cytokine modulation by 96. Sánchez-Bretaño A, Callejo M, Montero M, Alonso-Gómez ÁL, Delgado stress hormones and antagonist specific hormonal inhibition in rainbow MJ, Isorna E. Performing a hepatic timing signal: glucocorticoids trout (Oncorhynchus mykiss) and gilthead sea bream (Sparus aurata) head induce gper1a and gper1b expression and repress gclock1a and kidney primary cell culture. Gen Comp Endocrinol. (2017) 250:122–35. gbmal1a in the liver of goldfish. J Comp Physiol B (2016) 186:73–82. doi: 10.1016/j.ygcen.2017.06.005 doi: 10.1007/s00360-015-0936-2 76. Cavodeassi F. Dynamic tissue rearrangements during vertebrate eye 97. Martorell-Barceló M, Campos-Candela A, Alós J. Fitness consequences of morphogenesis: insights from fish models. J Dev Biol. (2018) 6:4 fish circadian behavioural variation in exploited marine environments. PeerJ. doi: 10.3390/jdb6010004 (2018) 6:e4814. doi: 10.7717/peerj.4814 77. Jamniczky HA, Barry TN, Rogers SM. Eco-evo-devo in the study of adaptive 98. Potok ME, Nix DA, Parnell TJ, Cairns BR. Reprogramming the maternal divergence: examples from Threespine Stickleback (Gasterosteus aculeatus). zebrafish genome after fertilization to match the paternal methylation Integr Comp Biol. (2015) 55:166–78. doi: 10.1093/icb/icv018 pattern. Cell (2013) 153:759–72. doi: 10.1016/j.cell.2013.04.030 78. Teles M, Soares AMVM, Tort L, Guimarães L, Oliveira M. Linking cortisol 99. Goll MG, Halpern ME. Chapter 5 - DNA methylation in zebrafish. response with gene expression in fish exposed to gold nanoparticles. Sci Total In: Cheng X, and Blumenthal RM, editors. Progress in Molecular Environ. (2017) 584–5:1004–11. doi: 10.1016/j.scitotenv.2017.01.153 Biology and Translational Science Modifications of Nuclear DNA 79. Harel I, Brunet A. The African Turquoise killifish: a model for exploring and Its Regulatory Proteins. London: Academic Press. p. 193–218. vertebrate aging and diseases in the fast lane. Cold Spring Harb Symp Quant doi: 10.1016/B978-0-12-387685-0.00005-6 Biol. (2015) 80:275–9. doi: 10.1101/sqb.2015.80.027524 100. Metzger DCH, Schulte PM. Epigenomics in marine fishes. Mar Genomics 80. Bhattacharya M, Ghosh S, Malick RC, Patra BC, Das BK. Therapeutic (2016) 30:43–54. doi: 10.1016/j.margen.2016.01.004 applications of zebrafish (Danio rerio) miRNAs linked with 101. Luyer JL, Laporte M, Beacham TD, Kaukinen KH, Withler RE, human diseases: a prospective review. Gene (2018) 679:202–11. Leong JS, et al. Parallel epigenetic modifications induced by hatchery doi: 10.1016/j.gene.2018.09.008 rearing in a Pacific salmon. Proc Natl Acad Sci. (2017) 114:12964–9. 81. Malmstrøm M, Matschiner M, Tørresen OK, Jakobsen KS, Jentoft S. Whole doi: 10.1073/pnas.1711229114 genome sequencing data and de novo draft assemblies for 66 teleost species. 102. Cavalieri V, Spinelli G. Environmental epigenetics in zebrafish. Epigenet Sci Data (2017) 4:160132. doi: 10.1038/sdata.2016.132 Chromat. (2017) 10:46. doi: 10.1186/s13072-017-0154-0 Frontiers in Endocrinology | www.frontiersin.org 11 February 2019 | Volume 10 | Article 62 Balasch and Tort Netting the Stress Responses in Fish 103. Mommer BC, Bell AM. Maternal experience with predation risk 123. Macnab V, Katsiadaki I, Tilley CA, Barber I. Oestrogenic pollutants promote influences genome-wide embryonic gene expression in threespined the growth of a parasite in male sticklebacks. Aquat Toxicol. (2016) 174:92– sticklebacks (Gasterosteus aculeatus). PLoS ONE (2014) 9:e98564. 100. doi: 10.1016/j.aquatox.2016.02.010 doi: 10.1371/journal.pone.0098564 124. Ellison A, Rodríguez López CM, Moran P, Breen J, Swain M, Megias 104. Sopinka N, Capelle P, Semeniuk CA, Love OP. Glucocorticoids in fish eggs: M, et al. Epigenetic regulation of sex ratios may explain natural variation, interactions with the environment, and the potential to shape variation in self-fertilization rates. Proc R Soc B Biol Sci. (2015) 282. offspring fitness. Physiol Biochem Zool. (2017) 90:15–33. doi: 10.1086/689994 doi: 10.1098/rspb.2015.1900 105. Grosell M, Farrell AP, Brauner CJ. Fish Physiology: The Multifunctional Gut 125. Consuegra S, López CMR. Epigenetic-induced alterations in sex-ratios in of Fish. London: Academic Press (2010). response to climate change: An epigenetic trap? BioEssays (2016) 38:950–8. 106. Evans DH, Piermarini PM, Choe KP. The multifunctional fish gill: doi: 10.1002/bies.201600058 dominant site of gas exchange, osmoregulation, acid-base regulation, 126. Kah O, Dufour S. Chapter 2 - conserved and divergent features of and excretion of nitrogenous waste. Physiol Rev. (2005) 85:97–177. reproductive neuroendocrinology in teleost fishes. In: Norris DO, and Lopez doi: 10.1152/physrev.00050.2003 KH, editors. Hormones and Reproduction of Vertebrates. London: Academic 107. Hutchings JA. Old wine in new bottles: reaction norms in salmonid fishes. Press. p. 15–42. doi: 10.1016/B978-0-12-375009-9.10002-5 Heredity (2011) 106:421–37. doi: 10.1038/hdy.2010.166 127. Buxton CD, Garratt PA. Alternative reproductive styles in seabreams (Pisces: 108. Conrad JL, Weinersmith KL, Brodin T, Saltz JB, Sih A. Behavioural Sparidae). Environ Biol Fishes (1990) 28:113–24. doi: 10.1007/BF00751031 syndromes in fishes: a review with implications for ecology 128. Benvenuto C, Coscia I, Chopelet J, Sala-Bozano M, Mariani S. Ecological and fisheries management. J Fish Biol. (2011) 78:395–435. and evolutionary consequences of alternative sex-change pathways in fish. doi: 10.1111/j.1095-8649.2010.02874.x Sci Rep. (2017) 7:9084. doi: 10.1038/s41598-017-09298-8 109. Patzner RA. Reproductive strategies of fish. In: Rocha MJ, Arukwe A and 129. Pauletto M, Manousaki T, Ferraresso S, Babbucci M, Tsakogiannis A, Louro Kapoor BG, editors. Fish Reproduction. Boca Raton, FL: CRC Press. p. B, et al. Genomic analysis of Sparus aurata reveals the evolutionary dynamics 325–64. of sex-biased genes in a sequential hermaphrodite fish. Commun Biol. (2018) 110. Erisman BE, Petersen CW, Hastings PA, Warner RR. Phylogenetic 1:119. doi: 10.1038/s42003-018-0122-7 perspectives on the evolution of functional hermaphroditism in teleost fishes. 130. Silva AT, Midwood JD, Aarestrup K, Pottinger TG, Madsen SS, Cooke SJ. Integr Comp Biol. (2013) 53:736–54. doi: 10.1093/icb/ict077 The influence of sex, parasitism, and ontogeny on the physiological response 111. Wootton RJ, Smith C. Reproductive Biology of Teleost Fishes. Oxford: John of European Eels (Anguilla anguilla) to an Abiotic Stressor. Physiol Biochem Wiley & Sons (2014). Zool. (2018) 91:976–86. doi: 10.1086/698689 112. Hendry AP, Kelly ML, Kinnison MT, Reznick DN. Parallel evolution of the 131. Zwollo P. The humoral immune system of anadromous fish. Dev Comp sexes? Effects of predation and habitat features on the size and shape of wild Immunol. (2018) 80:24–33. doi: 10.1016/j.dci.2016.12.008 guppies. J Evol Biol. (2006) 19:741–54. doi: 10.1111/j.1420-9101.2005.01061.x 132. Valero Y, Cuesta A, Cammarata M, Esteban M, Chaves-Pozo E, Valero Y, et al. 113. Ito MH, Yamaguchi M, Kutsukake N. Sex differences in intrasexual Immune-endocrine interactions in the fish gonad during infection: an open aggression among sex-role-reversed, cooperatively breeding door to vertical transmission. Fishes (2018) 3:24. doi: 10.3390/fishes3020024 cichlid fish Julidochromis regani. J Ethol. (2017) 35:137–44. 133. Chaves-Pozo E, García-Ayala A, Cabas I. Effects of sex steroids doi: 10.1007/s10164-016-0501-9 on fish leukocytes. Biology (2018) 7:E9. doi: 10.3390/biology7 114. Culumber ZW, Tobler M. Sex-specific evolution during the 010009 diversification of live-bearing fishes. Nat Ecol Evol. (2017) 1:1185–91. 134. Szwejser E, Verburg-van Kemenade BML, Maciuszek M, Chadzinska doi: 10.1038/s41559-017-0233-4 M. Estrogen-dependent seasonal adaptations in the immune response 115. Dargent F, Rolshausen G, Hendry AP, Scott ME, Fussmann GF. Parting ways: of fish. Horm Behav. (2017) 88:15–24. doi: 10.1016/j.yhbeh.2016. parasite release in nature leads to sex-specific evolution of defence. J Evol Biol. 10.007 (2016) 29:23–34. doi: 10.1111/jeb.12758 135. Barber I, Mora AB, Payne EM, Weinersmith KL, Sih A. Parasitism, 116. Lucon-Xiccato T, Bisazza A. Sex differences in spatial abilities and personality and cognition in fish. Behav Process. (2017) 141:205–19. cognitive flexibility in the guppy. Anim Behav. (2017) 123:53–60. doi: 10.1016/j.beproc.2016.11.012 doi: 10.1016/j.anbehav.2016.10.026 136. Moran NP, Mossop KD, Thompson RM, Chapple DG, Wong BBM. 117. Stephenson JF, Kinsella C, Cable J, van Oosterhout C. A further cost for Rapid divergence of animal personality and syndrome structure the sicker sex? Evidence for male-biased parasite-induced vulnerability to across an arid-aquatic habitat matrix. Oecologia (2017) 185:55–67. predation. Ecol Evol. (2016) 6:2506–15. doi: 10.1002/ece3.2049 doi: 10.1007/s00442-017-3924-2 118. Rambo CL, Mocelin R, Marcon M, Villanova D, Koakoski G, de Abreu 137. Dunlap KD, Tran A, Ragazzi MA, Krahe R, Salazar VL. Predators MS, et al. Gender differences in aggression and cortisol levels in zebrafish inhibit brain cell proliferation in natural populations of electric fish, subjected to unpredictable chronic stress. Physiol Behav. (2017) 171:50–4. Brachyhypopomus occidentalis. Proc Biol Sci. (2016) 283:20152113. doi: 10.1016/j.physbeh.2016.12.032 doi: 10.1098/rspb.2015.2113 119. Redfern JC, Cooke SJ, Lennox RJ, Nannini MA, Wahl DH, Gilmour 138. Dunlap KD. Fish Neurogenesis in context: assessing environmental KM. Effects of maternal cortisol treatment on offspring size, influences on brain plasticity within a highly labile physiology and responses to stress, and anxiety-related behavior in wild largemouth morphology. Brain Behav Evol. (2016) 87:156–66. doi: 10.1159/ bass (Micropterus salmoides). Physiol Behav. (2017) 180:15–24. 000446907 doi: 10.1016/j.physbeh.2017.08.001 120. Foo YZ, Nakagawa S, Rhodes G, Simmons LW. The effects of sex hormones Conflict of Interest Statement: The authors declare that the research was on immune function: a meta-analysis. Biol Rev Camb Philos Soc. (2017) conducted in the absence of any commercial or financial relationships that could 92:551–71. doi: 10.1111/brv.12243 be construed as a potential conflict of interest. 121. Roved J, Westerdahl H, Hasselquist D. Sex differences in immune responses: hormonal effects, antagonistic selection, and evolutionary consequences. Copyright © 2019 Balasch and Tort. This is an open-access article distributed Horm Behav. (2017) 88:95–105. doi: 10.1016/j.yhbeh.2016.11.017 under the terms of the Creative Commons Attribution License (CC BY). The use, 122. Stocchi V, Wang T, Randelli E, Mazzini M, Gerdol M, Pallavicini A, distribution or reproduction in other forums is permitted, provided the original et al. Evolution of Th2 responses: characterization of IL-4/13 in sea bass author(s) and the copyright owner(s) are credited and that the original publication (Dicentrarchus labrax L.) and studies of expression and biological activity. in this journal is cited, in accordance with accepted academic practice. No use, Sci Rep. (2017) 7:2240. doi: 10.1038/s41598-017-02472-y distribution or reproduction is permitted which does not comply with these terms. Frontiers in Endocrinology | www.frontiersin.org 12 February 2019 | Volume 10 | Article 62