Abstract

Background Extreme low temperatures impose severe physiological stress on aquatic crustaceans. Understanding the molecular mechanisms of cold adaptation is critical for improving stress resilience in key aquaculture species. This study employed integrated transcriptomic and metabolomic analyses to decipher sex-divergent neuroendocrine strategies in Cherax quadricarinatus under cold stress. Results Males rely on high basal antioxidant capacity for rapid JAK-STAT pathway activation to combat acute cold stress, whereas females maintain metabolic homeostasis through sustained pathway activation. This sexually dimorphic strategy is negatively regulated by C16-ceramide. Females relied on sustained JAK-STAT activation for transcriptional reprogramming, while males exhibited rapid metabolic remodeling and transient antioxidant mobilization. Crucially, the sphingolipid hub molecule C16-ceramide was coordinately downregulated in both sexes. Exogenous supplementation revealed C16-ceramide potently suppressed JAK-STAT genes and disrupted hepatopancreatic redox homeostasis in females, while triggering antioxidant collapse in males. Conclusions This study provides the first evidence of sexual dimorphism in JAK-STAT mediated cold adaptation in invertebrates, identifies C16-ceramide as a regulator of sex-specific defense strategies, and confirms the penetration of sexual dimorphism into conserved molecular stress response networks. Supplementary Information The online version contains supplementary material available at 10.1186/s13293-026-00892-y.