Long-term thermal challenge increases cortisol accumulation and enhances negative feedback regulation of the HPI axis in the European seabass (Dicentrarchus labrax).

As ectotherms, fishes are particularly sensitive to rising temperatures, which can alter physiological regulation, including stress responses. Previous studies have shown that temperature can modulate multiple molecular components of the hypothalamus-pituitary-interrenal (HPI) axis, which regulates cortisol production, the primary stress hormone in fishes. In this study, we investigated how long-term rearing under a control or a warm seasonal thermal regime modulated both the basal activity of the HPI axis throughout development, and its responsiveness to acute stress at a specific life stage in the European seabass (Dicentrarchus labrax). HPI-related gene expressions were developmentally structured and their thermal regulation occurred even at early life stage (i.e. all-fins). At later life stages (one- and two-year-old fish), an overall pattern emerged, indicating a general downregulation of key genes expression, espacially mr, in the warm regime, consistent with a negative feedback regulation of the HPI axis under prolonged thermal exposure. Fish reared in the warm regime also exhibited higher cortisol levels in scales mainly at two years of age, indicating sustained glucocorticoid exposures under this condition. Finally, following an acute confinement stress exposure, one-year-old fish reared in the warm regime exhibited an amplified cortisol response, suggesting exacerbated HPI-axis reactivity at elevated temperatures. Our findings provide new insights into how warming shapes molecular regulation and stress responsiveness of the stress physiology in ectotherms.