Comparative Transcriptomics Reveals Hypoxia-Modulated Transcriptional Responses to Vibrio parahaemolyticus Infection in Takifugu obscurus

The disease triangle posits that outbreaks arise from host–pathogen–environment interactions. In aquaculture, hypoxia and Vibrio infection often co-occur, yet how dissolved oxygen influences antibacterial immunity remains unclear. We examined how hypoxia and Vibrio parahaemolyticus infection, individually and in combination, reshape the liver transcriptome of Takifugu obscurus. Shared responses to hypoxia and infection included il15ra, smpd1, itga2, prkcb, map3k5, tp53inp1, and prdm1, involved in immune activation, phagocytosis, lymphocyte development, inflammation, and apoptosis. Under infection, hypoxia was associated with altered expression of inflammatory regulators (tcim, src, klf15, serpina3k, f2r, egr1, cebpb) and modules of heat shock, phosphatases, circadian rhythm, and cell cycle/survival. A 2 × 2 factorial analysis identified 15 genes with significant oxygen × infection interactions, and the number of infection-responsive DEGs was markedly reduced under hypoxia (592 vs. 11), indicating that hypoxia reshapes rather than simply adds to the infection response. We also re-analyzed previously published metabolomic data from our earlier study as supporting evidence; this re-analysis revealed changes in prostaglandin A2, cuminaldehyde, and long-chain acylcarnitines, which may be associated with inflammatory regulation. In vitro, hypoxia modulated infection-induced cytokine transcription: at 3 h post-infection, hypoxia suppressed infection-induced tnfa, il1b, and il6; at 6 h, oxygen × infection interactions were detected for tnfa and il1b, whereas il6 remained oxygen-insensitive. Collectively, this comparative transcriptomic analysis reveals hypoxia-modulated transcriptional responses to V. parahaemolyticus infection in T. obscurus, suggesting that hypoxia may perturb immune homeostasis and disease resistance in fish.