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A new immersed boundary Wall-Modelled Large Eddy Simulation (WMLES) formulation is developed to study high-lift aerodynamics on the NASA High-Lift Common Research Model (HL-CRM). A sequence of Cartesian Octree grids with sizes ranging from 100 Million through 2.02 Billion grid points is utilized to systematically assess grid-sensitivity and convergence for the in-tunnel (QinetiQ) configuration of the model, and remarkable agreement between the immersed boundary and the curvilinear body-aligned WMLES formulations is reported on grids with comparable resolutions. In the free-air configuration of the model, consistent predictions between the Curvilinear Overset and the Cartesian Octree formulations are reported for angles of attack up to C(L,max) at a=19.57. However, some differences in the onset of stall are seen between the two methods for a>20°: while the curvilinear WMLES experiences wing-root separation with increasing angle of attack (Topology A), the Cartesian Octree formulation shows a different flow topology characterized by boundary layer weakness on the main element, emanating from the pylon-wing attachment (Topology B). In order to obtain further insight into the two-distinct topologies, carefully designed numerical experiments to isolate effects of the model standoff and the tunnel wall-boundary layers are conducted using the immersed boundary WMLES formulation. The increased incidence angle-of-attack on the inboard portion of the wing due to the standoff is shown to be sufficient for triggering a switch from Topology B to Topology A in Cartesian WMLES. The role of the floor boundary layer is further examined in detail by identification of additional corner-flow vorticity generated by the viscous juncture flow interactions between the floor boundary layer and the standoff leading to formation of a strong coherent and persistent vortex on the belly-side of the fuselage. The intensity of this vortex is shown to increase with the thickness of the floor boundary layer. A further increase in the incidence angle of attack near the leading-edge strake caused by the presence of this belly-side vortex is quantified for two-distinct floor boundary layers. Both of the floor boundary layers considered result in the onset of large scale wing-root separation at a=21.47in non-confined (free-air) configurations.