Background: Non-specific interstitial pneumonia (NSIP), the second most common idiopathic interstitial pneumonia (IIP), lacks a clear understanding of its pathogenesis. To shed light on the molecular mechanisms underlying NSIP, we employed RNA-Sequencing of bronchoalveolar lavage (BAL) samples in this study.

Methods: BAL samples were collected from NSIP (n=5) patients and RNA-seq data of healthy individuals was downloaded from European nucleotide archives ENA (n=3). RNA- sequencing was performed and FASTQ data were processed for differential gene expression and functional enrichment analysis.

Results: We identified 17,883 differentially expressed genes (15,513 upregulated, 2,370 downregulated) including both protein-coding as well as non-coding genes. Histone cluster genes were among the most highly expressed genes while PTCSC1 was the most highly expressed lncRNA. Enrichment analysis showed neuroactive ligand-receptor interaction, calcium signaling, and ECM-receptor were among the upregulated pathways while hsv1 infection, metabolic and oxidative phosphorylation were among the negatively correlated pathways. cell adhesion, homophilic cell adhesion was among the top biological processes while ECM structural constituent, transmitter ion channel activity was among the top molecular functions. While most of the DEGs were mainly extracellular regions and spaces.

Conclusion: Our study has revealed many differentially expressed genes, both coding and non-coding, including highly expressed histone cluster genes and PTCSC1, and identified key pathways and processes involved in NSIP, highlighting the need for further research in intercellular communication and extracellular matrix.