Inhalation of carbon nanomaterials (NMs) can cause severe health effects, including chronic inflammation and fibrosis. Here, we analyzed the response to different carbon NMs (carbon black, double-walled (DWCNT), multi-walled carbon nanotubes (MWCNT)) in lungs of mice with single cell resolution by RNA sequencing to obtain .a better understanding of NM specific, pulmonary cell perturbation patterns.At the chosen doses, all NMs caused comparable airspace neutrophilia at 12h, which increased until day 6 for CNTs and remained elevated until day 28 for MWCNT. We observed a significant increase in total BAL macrophages exclusively after day 6 CNT instillation, coinciding with the loss of alveolar macrophages (AM) for MWCNTs, and to a lesser extent DWCNTs as determined in lung FACS analysis.In parallel, we noticed pulmonary accumulation of a transitional macrophage population at day 6 uniquely after MWCNT instillation, corresponding to the monocyte-derived macrophage population identified in experimental bleomycin- and asbestos-induced lung fibrosis (Misharin et al.,JEM,2017.214(8)). The pro-fibrotic role of this population also has been demonstrated in the context of SARsCoV2 infection-associated acute respiratory distress (Wendisch et al.,Cell,2021.184(26)). According to RNA velocity analysis, blood monocytes differentiated into Lyve1-/CD163- interstitial macrophages and subsequently gave rise to this transitional population that failed to replenish the CD11c+/SiglecFhigh AM pool.In conclusion, distinct environmental nanoparticles induce lung injury and reprogramming of macrophages that resemble pro-fibrotic macrophage activation in experimental and virus induced lung damage.