Macrophages are prototypic resident immune cells that shape a range of effects, from safeguarding homeostasis to inflammation, based on their remarkable plasticity and ability to adjust quickly to changing environmental cues. A panel of transcription factors and epigenetic regulators in conjunction with STAT1/3/6 define the state of the resident macrophages. Recent advances in transcriptional and chromatin profiling have opened an entirely new avenue. This new avenue investigates the environmental cues that define tissue-specific macrophage profiles in health and their dynamics upon stress/disease. Our major goal is to analyse the role of STAT1/3 in the in vivo homeostatic signature of alveolar macrophages (AM) and to investigate the hierarchy of changes in acute perturbations of homeostasis (such as after birth). We shall determine the transcriptional profile (RNASeq) and enhancer landscape of healthy adult pulmonary macrophages by genome-wide mapping of selected histone marks and open chromatin (Chip-Seq, ATAC-Seq). Within the project part, we aim to derive a detailed map of transcriptional and enhancer landscapes of AMs, and insights into the role of STAT1/3. We will provide an excellent basis for understanding the memory potential and functional impact of perturbations and will open ways to develop drugs to modulate macrophage activity in inflammatory diseases.