Ocean warming driven by climate change has led to an increased frequency of extreme high-temperature events, posing serious threats to marine organisms. Yellowfin tuna (Thunnus albacares), a pelagic species with partial endothermic traits, holds high ecological and economic value but remains highly sensitive to acute thermal stress. In this study, we simulated heatwave conditions in the South China Sea by exposing juvenile yellowfin tuna to 34 °C (high-temperature group, HT) and 28 °C (control group, LT), and analyzed hepatic transcriptomic responses at 6 h and 24 h. A total of 778 and 524 differentially expressed genes (DEGs) were identified at 6 h and 24 h, respectively, with 155 shared DEGs. KEGG enrichment analysis showed that these common DEGs were significantly associated with key pathways such as protein processing in the endoplasmic reticulum, herpes simplex virus 1 infection, and antigen processing and presentation. Clustering analysis revealed that classical stress-response genes, including hspa5, dnajc3a, hspa4l, and hsp90b1, were significantly upregulated under heat stress. Protein–protein interaction (PPI) analysis further confirmed these genes as central hubs within molecular chaperone and protein-folding modules. In contrast, immune-related genes such as MHC1, IFIH1, and KRAB were downregulated and showed weak or no interactions in the network. This study provides molecular insights into the thermal stress response of yellowfin tuna and offers a theoretical basis for the development of heat-resilient breeding strategies and improved aquaculture management.



