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Dengue infection is one of the most prevalent arthropod-borne viral diseases, which can result in severe complications. Identification of genes and long non-coding RNAs (lncRNAs) involved in dengue infection would help in deciphering potential mechanisms responsible for the disease progression. We comprehensively analyzed the dynamic transcriptome during dengue disease progression and identified critical genes and lncRNAs with expression perturbations. Our findings revealed that the expression of genes (i.e., CCR10 and GNG7) and lncRNAs (i.e., CTBP1-AS and MAFG-AS1) were potentially regulated by m6A RNA methylation. Interestingly, dengue viral proteins prevalently interact with genes or lncRNAs with expression perturbations, which are involved in cell cycle, inflammation signaling pathways and immune response. Dynamically expressed genes and lncRNAs were likely to locate in the central regions of human protein-protein network, which play crucial roles in mediating signaling spread and helping viral replication. Immune microenvironments analysis revealed that plasma cells levels were increased and T cells infiltrations were decreased during dengue disease progression. Dynamically expressed genes and lncRNAs were correlated with immune cell infiltrations. Moreover, network analysis reveals the associations between dengue viral infections and human complex diseases (i.e., digestive diseases and neoplasms). Our comprehensive transcriptome analysis of dengue disease progression identified potential gene and lncRNA biomarkers, providing novel insights for understanding the pathogenesis of and developing effective therapeutic strategies for dengue infection.