Background: Aestivation is one of the strategies used by sea cucumbers (Apostichopus japonicas) in order to improve survival in response to the high-temperature and droughty conditions. Previous studies have carried out to investigate the immune or physiological alterations at the aestivation stage. However, it lacks information on the relationship between immunity and physiology. Herein, transcriptome sequencing was used to study gene expression during the aestivation stage. The results of this study provide a comprehensive understanding of the molecular mechanisms that protect sea cucumbers from the high-temperature condition, which favors improving survival in cultured sea cucumbers. Results: The transcriptome analysis of dormant (aestivation) and revival sea cucumbers generated 2,368 differentially expressed genes (down-regulation: 927; up-regulation: 1,441) and 39,081 unchanged genes. Basing on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, the down-regulated genes of dormant group were identified to be involved in DNA replication, RNA metabolic process, protein modification and biosynthesis, macromolecule metabolism, and cellular metabolism, which resulted in the inhibition of motility, skeletal development, neural activity, cell proliferation and development of A. japonicas. In contrast, the up-regulated genes were associated with fatty acid metabolism, carbohydrate hydrolysis, and phagocytosis. Protein-protein interaction network analysis further revealed that carbohydrate hydrolysis promoted the phagocytosis activity in the dormant group. Furthermore, the expression pattern of all tested genes in qRT-PCR analysis fitted well with those in RNA-Seq, with the exception of FASNL, which was unchanged in the qRT-PCR but up-regulated in RNA-seq. Conclusions: During the dormant stage, sea cucumbers decreased DNA replication, transcription and translation to achieve a hypometabolic state beneficial for reducing energy consumption. On the contrary, fatty acid metabolism and carbohydrate hydrolysis were increased for energy supply. Moreover, high levels of carbohydrate hydrolysis promoted phagocytosis, which is a crucial innate immune response to infection by pathogens. These results provided new insight into potential molecular mechanisms that enable the sea cucumbers to respond to high temperatures. Keywords: Aestivation, Apostichopus japonicas, hypometabolism, fatty acid metabolism, carbohydrate hydrolysis, phagocytosis