Cross-species transmission of influenza A virus (IAV) represents a major risk for emergence of new pandemics, however, the host molecular responses invoked by cross-species IAV infection remain incompletely defined. MicroRNAs (miRNAs) are important post-transcriptional regulators of innate immunity, but their role during infection with IAV strains of the same subtype but of different host origin has not been investigated. Here, we investigated pulmonary miRNA responses in upper and lower lung sites from pigs inoculated with either a swine-adapted (swH1N1) or a human-adapted (huH1N1) IAV originating from the 2009H1N1 pandemic strain. High-throughput microfluidic RT-qPCR profiling of 115 miRNAs and selected antiviral genes revealed strain-dependent differences, with 33 miRNAs being differentially expressed in pig lungs (upper and lower lung) after human-adapted IAV infection, while only eight miRNAs were altered after swine-adapted IAV infection. Expression of several miRNAs correlated inversely with predicted target pattern recognition receptor (PRR) and interferon-stimulated gene (ISG) transcripts after huH1N1 infection, including miR-19a/b, miR-21-5p, and miR-93-3p, suggesting miRNA-mediated fine-tuning of antiviral signaling. Notably, extensive downregulation of miRNAs in the lower lungs after huH1N1 infection coincided with robust ISG induction, despite huH1N1 viral lung load being comparable to swH1N1 viral load. The swine-adapted IAV, in contrast, triggered stronger RIG-I-like receptor and cGAS transcription without substantial miRNA changes. Together, these findings demonstrate that pulmonary miRNA responses to IAV are both strain- and lung site-specific and may contribute to shaping the outcome of infection depending on the degree of viral host adaptation.