Abstract: 【Objective】To investigate regulatory mechanism of the responses to low temperature stress in wild tilapia,comparing to that of the cultured tilapia,so as to contribute to screen cold tolerant parents from wild tilapia in the future.【Method】A wild and a cultured tilapia populations with similar sizes were selected for a gradient low temperature stress test that the water temperature was decreased from 26℃ to 14℃ at the rate of 1℃/12 h and kept at 14℃ for 288 h(12 d). The brain tissues were collected at 26℃,20℃ and 14℃ for 0,120 and 288 h during this period,respectively,and were dissected. The prepared cDNA libraries were sequenced using Illumina HiSeq×Ten platform. A comparative transcriptome analysis was carried out to identify differentially expressed genes(DEGs)between the stressed and control tissues. Expression of the critical genes involved in the responses to low temperature stress were verified with a qRT-PCR analysis.【Result】Death of wild tilapia individuals initially occurred at 11℃ and still 50.0% of them were alive at 8℃,indicating that the wild tilapia had a better tolerance to low temperature than the cultured tilapia.During the long-term low temperature stress at 14℃,DEGs expression in cultured tilapia brain tissue was about 10 times higher than that in wild tilapia, indicating that the stress response of cultured tilapia was much stronger. KEGG pathway enrichment analysis results showed that the up-regulated DEGs of cultured GIFT tilapia and wild tilapia maintained at 14℃ for 120 and 288 h were both enriched in ribosome formation,endoplasmic reticulum protein processing and spliceosome signaling pathways. The up-regulated DEGs of wild tilapia were additionally enriched in nucleotide excision repair,N-glycosylation biosynthesis and DNA replication pathways. Compared with the cultured Tilapia,there were 577 unique DEGs in wild Tilapia,which were mainly enriched in the NOD receptor signaling pathway,apoptosis,endocytosis and other pathways. The NOD receptor signaling pathway was activated,and apoptosis was inhibited. In wild tilapia,the key functional genes involved in Nod-like receptor signal pathway,such as Nemo,NFκB,P38,JNK and IL-1β,maintained a high expression under the long-term low temperature stress. Meanwhile,the key genes employed in the endocytosis pathway had the much higher expression than the cultured tilapia.【Conclusion】Wild tilapia has stronger cold tolerance than cultured tilapia by avoiding excessive stress response and maintaining low-level metabolic cell stability to alleviate the damage of low temperature stress on the body,as well as continuing to activate NOD receptor signaling pathways and endocytosis pathways to maintain their immunity