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Air exposure is a common stress for <i>Corbicula fluminea</i>, an economically important freshwater shellfish consumed in China, during aquaculture and transportation. However, little is known about its molecular responses to air exposure. Therefore, this study used a combination of PacBio full-length and Illumina transcriptomes to investigate its molecular responses to air exposure. A total of 36,772 transcripts were obtained using PacBio sequencing. Structural analysis identified 32,069 coding sequences, 1906 transcription factors, 8873 simple sequence repeats, and 17,815 long non-coding RNAs. Subcellular localization analysis showed that most transcripts were located in the cytoplasm and nucleus. After 96-h of air exposure, 210 differentially expressed genes (DEGs) in the gill were obtained via Illumina sequencing. Among these DEGs, most of the genes related to glycolysis, tricarboxylic acid cycle, lipid metabolism, and amino acid metabolism were upregulated. Additionally, many DEGs associated with immunity, cytoskeleton reorganization, autophagy, and ferroptosis were identified. These findings indicated that metabolic strategy change, immune response, cytoskeleton reconstruction, autophagy, and ferroptosis might be the important mechanisms that <i>C. fluminea</i> use to cope with air exposure. This study will enrich the gene resources of <i>C. fluminea</i> and provide valuable data for studying the molecular mechanisms coping with air exposure in <i>C. fluminea</i> and other freshwater mollusks.