## 4 Discussion
### Linking Hg Contamination, Climate Change Stressors, and Potential Impacts on Seafood Safety
Nevertheless, various factors can concomitantly influence species' metabolic response to abiotic stressors, namely, feed availability, severity, and/or chronicity of the stressor, species' thresholds of physiological tolerance to shifts in abiotic conditions, and co-exposure to other environmental stressors, like pollutants [70; 81; 83]. In general, increased seawater temperatures are associated with enhanced metabolism, which can likely translate into either increased animal growth efficiency when sufficient amounts of feed/prey are available to meet animals' energetic demands or depressed growth (associated with lower K condition index values) when there is limited feed/prey availability [41; 70]. Acidification is also associated with depressed growth and poor animal fitness, and this is due to the high energetic resources that are required to maintain homeostatic balance and ionic exchanges under lower pH levels and, thus, that are no longer available to be used in other biological functions, like growth [81]. In the present study, despite _S. senegalensis_ exposed to climate change-related stressors and/or Hg exhibiting lower TL and W (only significant for CONT treatment), no significant variations in animal condition (K) were observed, which can be due to the facts that (i) benthic species, particularly pleuronectiforms usually have lower metabolism, compared to pelagic fish species [68], (ii) the amount of feed provided was enough to maintain the energetic requirements, even in warmer temperatures, and (iii) \(\Delta\)temperature = +4 \({}^{\circ}\)C and \(\Delta\)pH = -0.4 pH units still fell within the limits of physiological tolerance of _S. senegalensis_. Noteworthy, the increased Hg NAR and decreased Hg elimination under warming did not affect animals' condition, thus indicating that fish were still able to physiologically cope with the exposure to Hg (at the concentrations selected in this study, which were environmentally representative), even when abiotic stressors were combined and despite the biochemical changes elicited by stressors (acting alone or interacting with each other). Matching the trends reported in previous ecotoxicological studies (e.g., References [24; 26; 79; 80; 83]), the three studied stressors elicited differential neuro-oxidative responses in fish muscle, liver, and brain. Such differences can be mostly attributed to the fact that (i) each fish tissue is functionally and structurally different, thus having distinct baseline biomarker/enzyme levels and responding differently to environmental stressors, including their interactions [80], (ii) different Hg concentrations were reached in each tissue (i.e., liver > brain > muscle), and (iii) chemical contaminants, like the neurotoxic Hg, can have specific modes of action and target organs [64]. Hence, despite the significantly higher Hg concentrations found in the liver, the present findings show that neuro-oxidative responses triggered by Hg were more notorious in the brain (i.e., significant differences were found between non-contaminated and Hg contaminated fish in LPO, CAT, SOD, and AchE activities, and negative correlations between these variables and Hg NAR occurred in this tissue, a result that is consistent with the mode of action (neurotoxic) of this contaminant (e.g., Reference [84]). Another aspect worth mentioning is the fact that, in the present study, both up- and downregulations of the selected ecotoxicological biomarkers were observed, depending on the tissue and stressor interaction, a trend that is also in agreement with previous findings (e.g., References [24; 25; 80; 83; 85]). Such differential tissue biomarker responses to environmental stressors are a result of either (i) the activation of cells' defense mechanisms in order to overcome the stress (in case of biomarker upregulation) or (ii) the depletion of cellular defense mechanisms due to severe and/or long-lasting stress conditions that exceed species' thresholds of physiological tolerance (in case of biomarker downregulation) [24; 83].