Transcriptomic Traces of Noise Exposure in Hearing Loss and Systematic Identification of Biomarker Candidates at the Molecular Scale

Occupational noise-induced hearing loss (NIHL) is a common occupational disorder, yet non-invasive molecular indicators of chronic occupational noise exposure remain insufficiently characterized. Although the cochlear mechanisms behind NIHL have been extensively studied in experimental models, peripheral blood transcriptomic alterations in affected human populations are less well defined. In this exploratory study, we aimed to describe peripheral blood gene expression patterns associated with occupational NIHL and to generate candidate molecular signals for future validation. Peripheral blood RNA sequencing (RNA-seq) was performed in 11 male individuals with occupational bilateral sensorineural hearing loss and four noise-unexposed healthy male controls. Transcript abundance was quantified using a standardized RNA-seq workflow, and formal differential expression analysis was conducted on gene-level count data derived from Salmon quantification using DESeq2 with Benjamini–Hochberg correction. Through our analysis, we identified a limited set of differentially expressed genes, including upregulated interferon-associated transcripts, such as RSAD2, IFIT1, IFI44L, and CMPK2, host-defense-related genes, including DEFA1, DEFA3, and DEFA4, and immune-regulatory transcripts such as HLA-DRB1 and GPR15, together with downregulated non-coding RNAs including SNORD3A and SNORD3C. These findings suggest that occupational NIHL may be accompanied by detectable peripheral blood transcriptomic alterations, predominantly involving immune- and host-defense-related pathways. Given the limited cohort size and exploratory design, these genes represent preliminary candidates for validation in larger independent cohorts.