La Nina events caused by global climate change have amplified ocean temperature fluctuations, challenging aquaculture operations for species such as yellowfin tuna (Thunnus albacares), particularly under winter cooling conditions. To investigate the physiological responses of juvenile tuna, two experimental treatments low-temperature group (LT, 24 °C) and ultra-low-temperature group (ULT, 18 °C) were established and sampled at 0, 12, 24, and 36 h, alongside a 30 °C control group (CG). Transcriptomic analysis of the brain, red muscle, and white muscle revealed that, upon sensing low temperatures, the brain activated multiple immune, stress, and endocrine pathways, including TNF and Toll-like receptor signaling. In response to this activation, genes such as hspa5, hsp90aa1.2, STAT1, and CXCR2 showed altered expression, indicating their involvement in downstream stress and immune regulatory processes. Cold-stress signals were then transmitted to the muscles, which adapted via key genes linked to energy metabolism (glycolysis, gluconeogenesis, fatty acid oxidation), protein folding (HSPA1s), and myofiber remodeling (col6a2, PXN). Notably, responses were more pronounced at 18 °C. Muscle contraction-related genes (myl2b, myl13) collaborated with signaling molecules (SRC, PIK3CA_B_D) to form a stress-response network ensuring efficient energy supply, fiber stability, and contractile function. Furthermore, muscle-derived metabolites and stress proteins are fed back to the brain, establishing a cross-tissue, bidirectional regulatory loop that preserves energy provision, immune defense, and muscle integrity under cold stress. These findings advance our understanding of the molecular responses in yellowfin tuna to low-temperature conditions, offering valuable guidance for improving cold tolerance and optimizing aquaculture and ecological adaptation strategies.
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