Discussion

Stress can have profound effects on vertebrate immunity. Stress-induced changes in immune functions are typically orchestrated via hypothalamic–pituitary–adrenal (HPA) axes, particularly glucocorticoids hormones. However, glucocorticoid release and levels of immune activity exhibit diel variation, driven by the molecular circadian clock. Therefore, it is increasingly apparent that understanding this complex three-way interaction of stress, circadian rhythms and immunity, is pivotal to managing disease risks. Here, utilising a whole-transcriptome sequencing approach, we demonstrate that social stress in tilapia (Oreochromis niloticus) due to sub-optimal stocking conditions increases susceptibility to the oomycete Saprolegnia parasitica, via altered transcriptional responses to infection. Tilapia held at low densities have increased expression of genes related to stress, likely due to increased aggressive interactions. When challenged with Saprolegnia, low density fish exhibit reduced expression of inflammatory gene responses and higher levels of adaptive immune gene suppression, resulting in significantly higher mortality rates. In addition, Saprolegnia infection substantially perturbs expression of circadian clock genes and low density (high stress) fish have higher levels of molecular clock dysregulation. Our results reveal the impact of chronic social stress on transcriptional responses to infection and highlight the need to incorporate circadian infection biology into our understanding of disease dynamics in animals.